Combined expression of the non-receptor protein tyrosine kinases FAK and Src in primary colorectal cancer is associated with tumor recurrence and metastasis formation

Heer, Pieter de; Koudijs, Margaretha M.; Velde, Cornelis J.H. van de; Aalbers, Remco I.J.M.; Tollenaar, R.A.E.M.; Putter, Hein; Morreau, J.; Water, Bob van de; Kuppen, Peter J. K.

doi:10.1016/j.ejso.2008.05.003

Cited by 18 publications

(15 citation statements)

References 21 publications

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“…High levels of both FAK and Src can be indicative of poor prognosis and tumour recurrence in a variety of cancers 5 and these data have been interpreted to suggest that inhibitors of FAK may control cancer growth and progression. Indeed several reports have shown that inhibition of FAK, often in combination with the inhibition of other targets, can suppress tumour growth and metastasis [9][10][11] .…”

Section: Discussionmentioning

confidence: 99%

“…The overexpression of FAK in cancer cells, combined with it essential role in cell migration, has implicated this molecule as a positive regulator of cancer progression 5,54,55 . High levels of both FAK and Src can be indicative of poor prognosis and tumour recurrence in a variety of cancers 5 and these data have been interpreted to suggest that inhibitors of FAK may control cancer growth and progression.…”

Section: Discussionmentioning

confidence: 99%

“…FAK also has important non-kinase functions 3 . FAK is overexpressed in many human cancer cells and has thus emerged as an anticancer target [4][5][6][7][8] . This has led to the development of FAK inhibitors although off-target effects are apparent [9][10][11] .…”

mentioning

confidence: 99%

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Haematopoietic focal adhesion kinase deficiency alters haematopoietic homeostasis to drive tumour metastasis

et al. 2014

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Metastasis is the main cause of cancer-related death and thus understanding the molecular and cellular mechanisms underlying this process is critical. Here, our data demonstrate, contrary to established dogma, that loss of haematopoietic-derived focal adhesion kinase (FAK) is sufficient to enhance tumour metastasis. Using both experimental and spontaneous metastasis models, we show that genetic ablation of haematopoietic FAK does not affect primary tumour growth but enhances the incidence of metastasis significantly. At a molecular level, haematopoietic FAK deletion results in an increase in PU-1 levels and decrease in GATA-1 levels causing a shift of hematopoietic homeostasis towards a myeloid commitment. The subsequent increase in circulating granulocyte number, with an increase in serum CXCL12 and granulocyte CXCR4 levels, was required for augmented metastasis in mice lacking haematopoietic FAK. Overall our findings provide a mechanism by which haematopoietic FAK controls cancer metastasis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Haematopoietic focal adhesion kinase deficiency alters haematopoietic homeostasis to drive tumour metastasis

et al. 2014

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“…More recently a larger series of colorectal cancers with matched liver metastases was used to evaluate the correlation of FAK staining with clinical outcome. In this study, FAK staining was equivalent in primary and metastatic lesions, and elevated levels of FAK and Src were associated with a reduced time to recurrence (de Heer et al, 2008).…”

Section: Gastro-intestinal Tract Cancermentioning

confidence: 86%

PTK2 (PTK2 protein tyrosine kinase 2)

Schwock¹,

Dhani²

2012

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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“…In colon cancer, both FAK and Src are overexpressed in both primary tumors and liver metastases. While expression of neither alone is prognostic, the combined overexpression of both FAK and Src is predictive of a short time until recurrence of disease, but is not linked to patient survival (43) . Other studies have looked at tyrosine phosphorylation of FAK and Src in tumor samples, particularly the autophosphorylation sites of FAK and Src (generally indicative of activation) and sites on FAK that are substrates of Src phosphorylation (41,44) .…”

Section: Phosphatidylinositol 3 ′ -Kinasementioning

confidence: 99%

Focal adhesion kinase-regulated signaling events in human cancer

Fu¹,

Hall²,

Schaller

2012

BioMolecular Concepts

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Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase that is highly expressed or activated in many human cancers. Under specific scenarios, FAK can regulate cell proliferation, cell survival, cell migration and invasion, and has been implicated in the control of tumorigenesis and metastasis. FAK has both catalytic and scaffolding activity, and triggers downstream signals by activation of a number of pathways, including the Ras/mitogen-activated protein kinase pathway, the phosphatidylinositol 3'-kinase/Akt pathway, and Rho family GTPases. Recent evidence also suggests novel signaling interactions between FAK and p53. These signaling events were defined primarily from studies on cells in culture, and elucidating which of these signaling pathways are pathologically relevant downstream of FAK in human cancer remains an important goal in determining the molecular mechanisms of tumorigenesis and metastasis. This review discusses select evidence of these signaling pathways with an emphasis on studies linking these to animal models of cancer and human disease. The role of FAK in the process of epithelial-to-mesenchymal transition and in cancer stem cells and recent therapeutic advances targeting FAK are also discussed.

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Combined expression of the non-receptor protein tyrosine kinases FAK and Src in primary colorectal cancer is associated with tumor recurrence and metastasis formation

Cited by 18 publications

References 21 publications

Haematopoietic focal adhesion kinase deficiency alters haematopoietic homeostasis to drive tumour metastasis

Haematopoietic focal adhesion kinase deficiency alters haematopoietic homeostasis to drive tumour metastasis

PTK2 (PTK2 protein tyrosine kinase 2)

Focal adhesion kinase-regulated signaling events in human cancer

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